Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two devastating and lethal neurodegenerative diseases seen comorbidly in up to 15% of patients. Despite several decades of research, no effective treatment or disease-modifying strategies have been developed. We now understand more than before about the genetics and biology behind ALS and FTD, but the genetic etiology for the majority of patients is still unknown and the phenotypic variability observed across patients, even those carrying the same mutation, is enigmatic. Additionally, susceptibility factors leading to neuronal vulnerability in specific central nervous system regions involved in disease are yet to be identified. As the inherited but dynamic epigenome acts as a cell-specific interface between the inherited fixed genome and both cell-intrinsic mechanisms and environmental input, adaptive epigenetic changes might contribute to the ALS/FTD aspects we still struggle to comprehend. This chapter summarizes our current understanding of basic epigenetic mechanisms, how they relate to ALS and FTD, and their potential as therapeutic targets. A clear understanding of the biological mechanisms driving these two currently incurable diseases is urgent—well-needed therapeutic strategies need to be developed soon. Disease-specific epigenetic changes have already been observed in patients and these might be central to this endeavor.
|Title of host publication||Advances in Neurobiology|
|Number of pages||29|
|State||Published - 2018|
|Name||Advances in Neurobiology|
Bibliographical noteFunding Information:
We would like to thank Dr. Tamas Ordog, Director of the Epigenomics Translational Program at Mayo Clinic Center for Individualized Medicine for reviewing and providing critical input for this manuscript.
© Springer International Publishing AG, part of Springer Nature 2018.
- Amyotrophic lateral sclerosis
- Epigenetic modifications
- Frontotemporal dementia
- RNA-mediated regulation
ASJC Scopus subject areas
- Developmental Neuroscience
- Cellular and Molecular Neuroscience